TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18169	54730;54731;54732	chr2:178604182;178604181;178604180	chr2:179468909;179468908;179468907
N2AB	16528	49807;49808;49809	chr2:178604182;178604181;178604180	chr2:179468909;179468908;179468907
N2A	15601	47026;47027;47028	chr2:178604182;178604181;178604180	chr2:179468909;179468908;179468907
N2B	9104	27535;27536;27537	chr2:178604182;178604181;178604180	chr2:179468909;179468908;179468907
Novex-1	9229	27910;27911;27912	chr2:178604182;178604181;178604180	chr2:179468909;179468908;179468907
Novex-2	9296	28111;28112;28113	chr2:178604182;178604181;178604180	chr2:179468909;179468908;179468907
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCT
• RefSeq wild type template codon: GGA
• Domain: Fn3-20
• Domain position: 4
• Structural Position: 4
• Q(SASA): 0.2739
• Predicted PPI site: I

Reported SAVs

SNV	RS	DUET	PolyPhen-2	Condel	Rhapsody	REVEL	MVP	Source	MAF	Disease	Zygosity	Site annotation	mCSM PPI	Predicted PPI site	Comments	AFR	AMR	AMS	ASJ	EAS	EUR	FIN	MDE	NFE	SAS	OTH
P/H	rs2054202479	None	1.0	N	0.899	0.446	0.648488047482	gnomAD-3.1.2	6.58E-06	None	None	None	None	I	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
P/H	rs2054202479	None	1.0	N	0.899	0.446	0.648488047482	gnomAD-4.0.0	6.58094E-06	None	None	None	None	I	None	2.41499E-05	0	None	0	0	None	0	0	0	0	0
P/L	None	None	0.987	N	0.882	0.446	0.776041197187	gnomAD-4.0.0	2.05477E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.80026E-06	0	1.65898E-05
P/R	None	None	0.997	N	0.891	0.45	0.600640161457	gnomAD-4.0.0	6.84925E-07	None	None	None	None	I	None	0	0	None	0	0	None	1.87498E-05	0	0	0	0

Saturation Mutagenesis

SAV	AlphaMissense (IC)	AlphaMissense Class (IC)	AlphaMissense (N2AB)	AlphaMissense Class (N2AB)	mCSM	mCSM class	PolyPhen-2	PolyPhen-2 Class	Rhapsody	Rhapsody Class	Condel	Condel Score	Site annotation	mCSM PPI	Predicted PPI site
P/A	0.0951	likely_benign	0.086	benign	-1.567	Destabilizing	0.117	N	0.53	neutral	N	0.494945794	None	None	I
P/C	0.58	likely_pathogenic	0.5995	pathogenic	-1.065	Destabilizing	0.999	D	0.913	deleterious	None	None	None	None	I
P/D	0.8316	likely_pathogenic	0.8115	pathogenic	-1.698	Destabilizing	0.998	D	0.877	deleterious	None	None	None	None	I
P/E	0.4733	ambiguous	0.4682	ambiguous	-1.723	Destabilizing	0.995	D	0.871	deleterious	None	None	None	None	I
P/F	0.6697	likely_pathogenic	0.6328	pathogenic	-1.318	Destabilizing	0.999	D	0.913	deleterious	None	None	None	None	I
P/G	0.5143	ambiguous	0.5079	ambiguous	-1.853	Destabilizing	0.966	D	0.853	deleterious	None	None	None	None	I
P/H	0.4044	ambiguous	0.3842	ambiguous	-1.392	Destabilizing	1.0	D	0.899	deleterious	N	0.505138667	None	None	I
P/I	0.4388	ambiguous	0.4076	ambiguous	-0.882	Destabilizing	0.995	D	0.895	deleterious	None	None	None	None	I
P/K	0.4233	ambiguous	0.4419	ambiguous	-1.27	Destabilizing	0.995	D	0.877	deleterious	None	None	None	None	I
P/L	0.2868	likely_benign	0.2557	benign	-0.882	Destabilizing	0.987	D	0.882	deleterious	N	0.520026918	None	None	I
P/M	0.4509	ambiguous	0.4443	ambiguous	-0.668	Destabilizing	1.0	D	0.9	deleterious	None	None	None	None	I
P/N	0.6604	likely_pathogenic	0.6339	pathogenic	-1.044	Destabilizing	0.998	D	0.882	deleterious	None	None	None	None	I
P/Q	0.2599	likely_benign	0.248	benign	-1.29	Destabilizing	0.998	D	0.875	deleterious	None	None	None	None	I
P/R	0.2907	likely_benign	0.2864	benign	-0.696	Destabilizing	0.997	D	0.891	deleterious	N	0.48929891	None	None	I
P/S	0.2261	likely_benign	0.2176	benign	-1.499	Destabilizing	0.987	D	0.848	deleterious	N	0.470434186	None	None	I
P/T	0.2617	likely_benign	0.237	benign	-1.428	Destabilizing	0.993	D	0.862	deleterious	N	0.501415684	None	None	I
P/V	0.3053	likely_benign	0.294	benign	-1.077	Destabilizing	0.99	D	0.868	deleterious	None	None	None	None	I
P/W	0.875	likely_pathogenic	0.8646	pathogenic	-1.47	Destabilizing	1.0	D	0.873	deleterious	None	None	None	None	I
P/Y	0.6866	likely_pathogenic	0.6658	pathogenic	-1.203	Destabilizing	1.0	D	0.915	deleterious	None	None	None	None	I

Titin has multiple isoforms, the longest being the theoretical IC (inferred complete) isoform which contains all 363 in-frame titin exons. Here all isoform positions have been mapped onto the IC sequence, with an exception being the C-terminal of the much shorter novex-3 isoform. This contains the out of frame exon 48 which cannot be mapped to the other isoforms.